Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading

• Type of Material: Article
• Authors: Sruti Bheri, Georgia Institute of Technology; Brandon P. Kassouf, Georgia Institute of Technology; Hyun-Ji Park, Georgia Institute of Technology; Jessica R. Hoffman, Georgia Institute of Technology; Michael Davis, Emory University
• Language: English
• Date: 2021-11-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/jcdd8110135
• Title of Journal or Parent Work: JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
• Volume: 8
• Issue: 11
• Grant/Funding Information: This study was supported by the Robert P. Apkarian Integrated Electron Microscopy Core (IEMC) at Emory University, which is subsidized by the School of Medicine and Emory College of Arts and Sciences. Additional support was provided by the Georgia Clinical and Translational Science Alliance of the National Institutes of Health under award number UL1TR000454. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.; This research was funded by the National Institutes of Health, grant number R01-HL145644 (MED).
• Keywords: microRNA-126; LIPOSOMES; exosome; Cardiovascular System & Cardiology; thin-film hydration; SYSTEMS; vesicle engineering; Cardiac & Cardiovascular Systems; PACLITAXEL; cardiac ckit plus progenitor cell; Life Sciences & Biomedicine; cardiac repair; Science & Technology; extracellular vesicle; CELLS; EXOSOMES
• Research Categories: Biology, Genetics; Biology, Cell; Health Sciences, Medicine and Surgery

Abstract

Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carry cardioprotective cargo, including microRNA (miRNA), within a complex membrane and improve cardiac outcomes similar to that of their parent cells. However, miRNA loading efficiency is low, and sEV yield and cargo composition vary with parent cell conditions, minimizing sEV potency. Synthetic mimics allow for cargo-loading control but consist of much simpler membranes, often suffering from high immunogenicity and poor stability. Here, we aim to combine the benefits of sEVs and synthetic mimics to develop sEV-like vesicles (ELVs) with customized cargo loading. We developed a modified thin-film hydration (TFH) mechanism to engineer ELVs from CPC-derived sEVs with pro-angiogenic miR-126 encapsulated. Characterization shows miR-126+ ELVs are similar in size and structure to sEVs. Upon administration to cardiac endothelial cells (CECs), ELV uptake is similar to sEVs too. Further, when functionally validated with a CEC tube formation assay, ELVs significantly improve tube formation parameters compared to sEVs. This study shows TFH-ELVs synthesized from sEVs allow for select miRNA loading and can improve in vitro cardiac outcomes.